Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.
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PMID:Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies. 917 29

Posttransplant lymphoproliferative disorders are typically of B cell origin, whereas T cell lymphomas have been rarely documented. We present a case of a non-Hodgkin's T cell lymphoma involving the intestinal graft of a multivisceral transplant patient. The patient was a 7-year-old girl who underwent at age 5 a multivisceral transplant secondary to short gut syndrome. Baseline immunosuppressive therapy consisted of FK506, methylprednisone, and mycophenolate mofetil. At 2 years posttransplant she presented with fever, diarrhea, nausea, and vomiting. Multiple endoscopic biopsies revealed a severe intensity, diffuse and focally nodular lymphocytic infiltrate composed predominantly of small, monomorphic lymphoid cells with scattered plasma cells and abundant eosinophils. Immunohistochemically, the majority of the lymphoid cells expressed the pan T cell marker CD3. Southern blot analysis revealed rearrangement of the T cell receptor beta chain gene, with germline configuration of the heavy immunoglobulin chain gene, confirming a clonal T cell genotype. In situ hybridization for Epstein Barr virus revealed rare positive lymphoid cells, that were negative with CD3 by immunohistochemical staining. A detailed clinico-radiological work-up revealed no other sites of involvement by the lymphomatous process. After the diagnosis of posttransplant lymphoproliferative disorder, immunosuppression was reduced with a subsequent partial improvement in the endoscopic appearance of the graft and a focal decrease in the lymphocytic infiltrate seen in the follow-up biopsies. Repeat gene rearrangement studies demonstrated germline configuration of both the T cell receptor beta chain gene and the heavy chain immunoglobulin. gene. To our knowledge, this represents the first description of a T cell lymphoma affecting the intestinal allograft of a multivisceral transplant patient.
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PMID:T cell lymphoma involving the graft of a multivisceral organ recipient. 1055 42

Lymphoproliferative disorders associated with the Epstein-Barr virus (EBV) include non-Hodgkin's lymphoma, Hodgkin's lymphoma, and "post-transplant lymphoproliferative disorders" (PTLD), which occur with immunosuppression after marrow and organ transplantation. PTLD is characterized by actively proliferating, latently infected EBV(+) B-lymphocytes, and often manifests a rapidly progressive fatal clinical course if the immunosuppression cannot be reversed. Lung transplant recipients are a subset of patients at special risk for developing PTLD. The incidence of PTLD development in these patients has been estimated at 5--10%. Whereas immunologic and antiviral therapy have been moderately effective for treating EBV-associated infections in the lytic phase, they have been less useful in the more common latent phase of the disease. One common treatment for herpesvirus infections has targeted the virus-specific enzyme thymidine kinase (TK). The lack of viral TK expression in EBV(+) tumor cells, due to viral latency, makes anti-viral therapy alone ineffective as an anti-neoplastic therapy, however. We have developed a strategy for the treatment of EBV-associated lymphomas/PTLD using pharmacologic induction of the latent viral TK gene and enzyme in the tumor cells, followed by treatment with ganciclovir. Arginine butyrate selectively activates the EBV TK gene in latently EBV-infected human lymphoid cells and tumor cells. A Phase I/II trial has been initiated, employing an intra-patient dose escalation of arginine butyrate combined with ganciclovir. In six patients with EBV-associated lymphomas or PTLD, all of which were resistant to conventional radiation and/or chemotherapy, this combination produced complete clinical responses in four of six patients, with a partial response occurring in a fifth patient. Pathologic examination in two of three patients demonstrated complete necrosis of the EBV lymphoma, with no residual disease, following a single three-week course of the combination therapy. Possible side-effects of the therapy included nausea and reversible lethargy at the highest doses. One patient suffered acute liver failure, thought to be secondary to release of FasL from the necrotic tumor. Analysis of patient-derived tumor cells in culture demonstrated that arginine butyrate produced selective induction of the EBV TK gene, which then conferred sensitivity to ganciclovir, resulting in tumor apoptosis. Additional patient accrual is sought for further evaluation of this therapy.
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PMID:Epstein--Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. 1149

Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell-mediated cytotoxicity. Campath-1H has been used in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade non-Hodgkin's lymphoma (LGNHL). Campath-1H is administered intravenously thrice weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete [CR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patients, responses are of the order of approximately 40%, with 2-4% CRs. Responses are more prominent in the blood and bone marrow compared to the lymph nodes. The median duration of response is 9-12 mo. Because of the antibody's higher activity on circulating lymphocytes, it has been used for in vivo purging of residual disease in B-CLL, followed by autologous stem-cell transplantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%. Promising results have been reported in a small number of patients with refractory autoimmune thrombocytopenia of lymphoproliferative disorders. The main complications of Campath-1H treatment are caused by tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 release, usually during the first intravenous infusion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent infusions and can be prevented by paracetamol and antihistamines. Immunosupression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections. More clinical trials in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders.
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PMID:Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders. 1177 65

Psoriasis is a chronic, debilitating skin condition that affects millions of people and is attributed to both genetic and environmental factors. Topical therapy is generally considered to be the first-line treatment of psoriasis. However, many patients do not respond to topical therapy or have disease so extensive that topical therapy is not practical. For these patients, systemic therapy is indicated. Presently, there are four available systemic treatments, psoralen with ultraviolet A (PUVA), methotrexate, oral retinoids (acitretin), and cyclosporin. Unfortunately, all of these treatments have significant potential adverse effects. PUVA may acutely cause nausea, pruritus and sunburn. More chronic and concerning is the development of PUVA lentigines, ocular complications and skin cancer. Non-melanoma skin cancer has been directly linked to PUVA; however, the association with melonoma is more elusive. Methotrexate use most notably carries the risk of hepatic fibrosis and cirrhosis, which is not always evident on liver function tests. Other more rare, but potentially life-threatening adverse effects include pancytopenia, lymphoproliferative disorders and acute pneumonitis. The addition of folic acid may help to reduce the risk of increasing liver enzymes and haematological toxicity seen in those taking methotrexate. Both methotrexate and oral retinoids are teratogenic and should never be used in pregnancy. Oral retinoids are probably the least effective available systemic medication for the treatment of plaque psoriasis. The effects are improved with the addition of other systemic therapies. Acitretin has replaced the formerly used etretinate primarily because of the significantly shorter half-life. The adverse effects are generally mild and reversible, making the drug fairly safe for long-term use. The most commonly seen adverse effects include elevated serum lipids, generalised xerosis and alopecia. Bony abnormalities, while somewhat controversial, have also been described and include diffuse idiopathic skeletal hyperostosis, skeletal calcifications and osteoporosis. Cyclosporin is the most recently approved systemic medication for plaque psoriasis. The nephrotoxicity associated with the use of cyclosporin can be minimised when used in lower doses and for a limited duration. Hypertension is usually mild and can be seen in up to about one-third of patients receiving long-term therapy. Cutaneous and internal malignancies have also been reported with cyclosporin and tend to be correlated with duration of treatment. In this review, we will examine the potential adverse effects with these US Food and Drug Administration-approved treatments in adults, with specific emphasis on the controversies that surround long-term therapy with these agents and their cumulative adverse effects.
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PMID:Comparative tolerability of systemic treatments for plaque-type psoriasis. 1238 Dec 13

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
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PMID:The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation. 1241 88

Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.
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PMID:Gastrointestinal complications in renal transplant recipients. 1591 Feb 87

Although bendamustine has been used to treat lymphoproliferative disorders for decades, it has only recently been approved for use in Canada. Thus, Canadian recommendations on the administration of bendamustine and the management of common adverse events (aes) are needed. This article highlights effective management and assessment strategies recommended by Canadian nurses and pharmacists for the most common aes arising from the use of bendamustine in patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Those strategies include administering bendamustine over 60 minutes instead of 30 minutes, administering pre-medications to control infusion-related reactions and nausea, hydrating patients to minimize fatigue, and using free-flowing saline at the closest port to prevent phlebitis.
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PMID:A Canadian perspective on the safe administration of bendamustine and the prevention and management of adverse events. 2452 3

Fever of unknown origin is a rare condition after solid organ transplant and is generally associated with atypical infections (eg, tuberculosis, fungal infections) and/or lymphoproliferative disorders. Here, we present a kidney transplant patient with a late diagnosis of E148Q mutation-positive familial Mediterranean fever as the cause of fever of unknown origin. A 22-year-old female patient with a previous history of 4 years of hemodialysis and unknown primary renal disease received a deceased-donor kidney transplant at our center 5 years previously. She had an uneventful course in the first 3 years following transplant. After this period, she was hospitalized 3 times during a 4-month period with fever, nausea, vomiting, and atypical abdominal pain. At that time, hemogram results were unremarkable, except for mild leukocytosis and slightly elevated acute-phase reactants; blood, urine, and throat cultures were negative, and there were no remarkable findings on imaging tests. Fever was controlled within 48 hours by administering empiric ampicillin-sulbactam therapy and discontinuing immunosuppressive treatment except steroids. Three successive hospital admissions owing to similar complaints suggested periodic fever syndrome, and therapy with 1 g/day colchicine led to an excellent clinical response with no recurrence of fever or other symptoms. An FMF gene mutation analysis revealed heterozygous E148Q mutation positivity. Continuing the current treatment regimen, the patient did well during at approximately 1.5 years of follow-up. In the Mediterranean region population, familial Mediterranean fever should be considered in the diagnosis of fever of unknown origin in patients who have undergone renal transplant. E148Q mutation-positive familial Mediterranean fever has a subclinical course and renal manifestations that differ from AA amyloidosis during childhood and may be responsible for de novo familial Mediterranean fever after renal transplantation.
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PMID:Late Diagnosis of E148Q Mutation-Positive Familial Mediterranean Fever in a Kidney Transplant Patient With Fever of Unknown Origin: A Case Report. 2826 Apr 82

Objective Primary retroperitoneal involvement of lymphoproliferative disorders is rare. Diffuse large B cell lymphoma (DLBCL) in the retroperitoneum has been scarcely reported and the diagnostic workup is challenging due to difficulties in access for tissue acquisition. Materials and methods A 73-year-old female presented with epigastric pain and nausea. A computed tomography scan revealed retroperitoneal lymphadenopathy. An EUS-FNA was performed and a cytological diagnosis of lymphomatous disorder was made on direct smears .A panel of immunocytochemical markers was applied on cell block preparations and revealed a EBV related DLBCL (CD20 positive, PAX-5 positive, CD3 negative, MUM-1 positive, BCL-2 positive, BCL-6 positive, CD10 positive, MIB-1 positive, and LMP-1 positive). Conclusion Our case illustrates the utility of EUS-FNA in the work-up of retroperitoneal lymphadenopathy and the importance of cell block processing in the diagnostic approach of EBV related DLBCL.
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PMID:Diagnosis and immunocytochemical characterization of an EBV related diffuse B Large cell lymphoma of the retroperitoneum from cell block preparations obtained by means of EUS guided FNA. 3323 5


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